Evaluation of bisindole as potent β-glucuronidase inhibitors: Synthesis and in silico based studies

Bisindole analogs 1-17 were synthesized and evaluated for their in vitro beta-glucuronidase inhibitory potential. Out of seventeen compounds, the analog 1 (IC50 = 1.62 +/- 0.04 mu M), 6 (IC50 = 1.86 +/- 0.05 mu M), 10 (IC50 = 2.80 +/- 0.29 mu M), 9 (IC50 = 3.10 +/- 0.28 mu M), 14 (IC50 = 4.30 +/- 0.08 mu M), 2 (IC50 = 18.40 +/- 0.09 mu M), 19 (IC50 = 19.90 +/- 1.05 mu M), 4 (IC50 = 20.90 +/- 0.62 mu M), 7 (IC50 = 21.50 +/- 0.77 mu M), and 3 (IC50 = 22.30 +/- 0.02 mu M) showed superior b-glucuronidase inhibitory activity than the standard (D-saccharic acid 1,4-lactone, IC50 = 48.40 +/- 1.25 mu M). In addition, molecular docking studies were performed to investigate the binding interactions of bisindole derivatives with the enzyme. This study has identified a new class of potent beta-glucouronidase inhibitors. (C) 2014 Elsevier Ltd. All rights reserved.